System with optical and electrical sensors for characterizing effluents from peritoneal dialysis patients

Abstract

A system for characterizing an effluent sample from a patient receiving peritoneal dialysis is provided. The system is equipped with a container (30) for accommodating an effluent sample, an optical system, an electrical system and a processor (13). The optical system is equipped with a light source (18, 24) and a photodetector (14, 54), the light source emitting a beam of radiation passing through the container and illuminating the effluent sample, and the photodetector detecting the radiation after illuminating the effluent sample to generate a light signal. The electrical system is equipped with at least one pair of electrodes (38a, 38b) attached to the container and arranged to measure an electrical characteristic of the effluent sample to generate a characteristic signal. The processor runs an algorithm that comprehensively processes the light signal and the characteristic signal to characterize the effluent sample.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to systems for monitoring patients in a hospital setting and a home setting, in particular systems for monitoring patients with end-stage renal disease (herein "ESRD") and receiving peritoneal dialysis (herein "PD") in a hospital setting and a home setting. BACKGROUND

[0002] PD is a dialysis that uses the peritoneum of a patient's abdominal cavity as a membrane through which fluid and dissolved substances are exchanged with the blood. PD is commonly used to remove excess fluid, correct electrolyte problems, and remove toxins from patients with ESRD. PD is generally less efficient than hemodialysis (herein "HD") in removing waste from the body. However, the efficacy of PD is generally superior to HD in the first few years of treatment. PD allows patients to be more active, produces less symptomatic fluctuations due to its continuous nature, and is better at removing phosphate compounds than HD. However, PD also generally removes a significant amount of albumin, which results in the need for continuous monitoring of the patient's nutritional status. The cost associated with PD is generally lower than that of HD in most parts of the world; this is particularly evident in developed economies. Other advantages of PD include greater flexibility and better tolerance by patients with severe heart disease.

[0003] PD can be performed at fixed intervals throughout the day (known as continuous ambulatory peritoneal dialysis (herein "CAPD")), or at night with the aid of a machine (known as an automated peritoneal dialysis machine (herein "APD") or 'cycler'). The solution is typically made of sodium chloride, bicarbonate, and an osmotic agent such as glucose.

[0004] During PD, dialysis solution (also referred to herein as dialysate or dialysis fluid) is introduced through a permanent catheter deployed in the patient's lower abdominal cavity during surgery. One end of the catheter is inserted into the abdominal cavity and the other end protrudes from the skin. As expected, the presence of the catheter creates a risk of peritonitis, as the catheter introduces bacteria into the abdominal cavity. Typically, 2-3 liters of dialysis solution is introduced into the abdominal cavity at the start of PD treatment. This volume, referred to as the "fill volume", can be up to 3 liters, and can also have medication added to the solution immediately prior to infusion. This volume remains in the abdominal cavity, and waste products diffuse from the underlying blood vessels across the peritoneum. After a variable period of time, the "dwell time" (typically 2-6 hours, depending on the treatment), the fluid is removed - the removed fluid is referred to as 'effluent'. The removal of effluent can occur automatically while the patient is sleeping (e.g., during APD), or during the day by exchanging the fluid 4-6 times per day (CAPD) while always maintaining 2 liters of fluid in the abdominal cavity. APD cycles 3-10 dwell periods per night, while CAPD involves 4 dwell periods per day, 2-3 liters per dwell period, with each fluid left in the abdominal cavity for 4-8 hours.

[0005] PD effluent can be monitored to determine whether the patient has early peritonitis or some other deleterious condition, which can affect the color of the effluent, for example. For example, pink effluent suggests internal bleeding or menstruation in the abdominal cavity, while the presence of brown or yellow effluent can indicate fecal matter, which in turn suggests intestinal perforation. Cloudy effluent typically suggests infection. Typically, the test used to determine this condition is to hold the waste bag containing the effluent above a typically legible document (e.g., a magazine or newspaper), and determine whether the text is legible. A document that cannot be clearly read indicates that the effluent is cloudy, which in turn can indicate the presence of white blood cells (e.g., leukocytes) or other biological matter, suggesting peritonitis. Thus, the assessment of PD effluent is a manual process that is difficult to repeat with any meaningful degree of accuracy. The subjectivity of the process, requiring a particular individual to make the visual assessment, further impacts the overall accuracy of the process.

[0006] Some automated systems have been developed for assessing PD effluent. For example, these systems include optical systems that characterize PD effluent based on light absorption, scattering, or fluorescence; other systems that measure results that describe chemical properties of the effluent, such as pH. In other examples, systems in the art measure physiological properties from a patient (e.g., blood pressure, blood glucose) to assess their condition (e.g., presence of peritonitis). Issued patents in this area include, for example: U.S. Patent 11,013,843; U.S. Patent 10,983,124; U.S. Patent 10,925,549; U.S. Patent 10,758,659; U.S. Patent 10,744,253; U.S. Patent 10,537,673; U.S. Patent 10,155,081; U.S. Patent 10,010,289; U.S. Patent 9,518,914; U.S. Patent 9,215,985; U.S. Patent 9,125,989; U.S. Patent 8,945,936; and U.S. Patent 8,801,652.

[0007] In view of the above, it would be beneficial to improve conventional methods for monitoring PD effluent from ESRD patients with the goal of determining conditions such as peritonitis as early as possible. SUMMARY

[0008] The technical solution described herein provides an automated quantitative measurement system for detecting white blood cells and other biological substances in PD effluent. In this way, the technical solution enables detection of infections and other conditions of a patient's abdominal cavity, such as peritonitis, bleeding, presence of fecal matter, at an early stage, thereby allowing a clinician to intervene and provide appropriate measures (e.g., prescribe antibiotics). Ultimately, this means that the system can help identify such infections, and allow such infections to be resolved or even ameliorated, thereby allowing the patient to continue PD treatment, and avoid HD treatment. This can be advantageous, as HD is typically relatively expensive, uncomfortable, and inconvenient for the patient. The system performing these measurements, referred to herein as a PD effluent analysis system (referred to herein as PDEAS), can be equipped with optical sensors, impedance sensors, and other sensors that measure PD effluent directly in the PD machine, but also in the tubing that drains PD effluent from the patient (into e.g. a toilet). The PDEAS is a compact, low-cost system that requires little or no interaction from the user. After measuring time-dependent waveforms with its various sensors, the PDEAS analyzes this data and transmits information directly to the APD (e.g. for dynamic control by the APD); additionally or alternatively, the PDEAS can transmit information to the cloud, either directly (e.g. through an internal cellular modem or Wi-Fi chipset), or through the user's device (e.g. a phone, tablet). In the cloud, algorithms can analyze the information, facilitate early detection of peritonitis and other health conditions, and pave the way for early clinical measures before these conditions worsen.

[0009] In view of the above, in one aspect, the present disclosure relates to a system for characterizing an effluent sample from a patient receiving PD. The system is generally equipped with a container for housing the effluent sample, an optical system, an electrical system, and a processor. The optical system is equipped with a light source and a photodetector, wherein the light source emits a beam of radiation that passes through the container and illuminates the effluent sample, and the photodetector detects radiation (e.g. scattered radiation) after illuminating the effluent sample to generate an optical signal. The electrical system is equipped with at least one pair of electrodes that are attached to the container and arranged to measure an electrical signal (e.g. capacitance) of the effluent sample to generate a measured electrical response (e.g. a capacitance signal). The processor, for example, runs an algorithm that processes the optical signal and the electrical signal in combination to characterize the effluent sample. However, it will be appreciated that other electrical signals (in addition to capacitance) are likewise contemplated herein, as disclosed in greater detail below. The at least one pair of electrodes can be attached to the container directly or indirectly.

[0010] In embodiments, the container is a cuvette comprising at least two surfaces. Each of these surfaces of the cuvette can comprise an optically transparent material, such as a material composed of glass, plastic, ceramic, diamond-based materials, or derivatives thereof. The electrodes are typically thin films, and ideally thin films that are both optically transparent and electrically conductive, deposited on at least one of the two surfaces. For example, in embodiments, the thin films are composed primarily of gold. In other embodiments, the thin films comprise In2O5Sn or derivatives thereof (e.g., indium tin oxide, herein “ITO”). Alternatively, the thin films are composed of thin metals that have reasonable transparency to wavelengths of light in the infrared, visible, and ultraviolet spectral ranges.

[0011] In embodiments, both the first and second surfaces of the cuvette comprise optically transparent electrodes. Here, the light source is configured to emit a beam of radiation through the first optically transparent electrode and into the effluent sample, and the photodetector is configured to receive radiation after illuminating the effluent sample and then passing through the second optically transparent electrode. The electrical system integrated with such a system can be equipped with a capacitor comprising two capacitor electrodes, the first optically transparent electrode being the first capacitor electrode and the second optically transparent electrode being the second capacitor electrode.

[0012] In related embodiments, the electrical system comprises a first pair of electrodes and a second pair of electrodes, where both the first and second pairs of electrodes comprise optically transparent openings (e.g., cutout regions in otherwise continuous electrically conductive regions), rather than being entirely optically transparent. Here, the light source is configured to emit a beam of radiation through a first optically transparent opening in the first electrode and into the effluent sample, and the photodetector is configured to receive radiation after illuminating the effluent sample and then passing through a second optically transparent opening in the second electrode.

[0013] In related embodiments, the optical system is further configured to measure light absorption by the effluent sample, such as a multi-frequency absorption spectrum. Here, the light source is configured to emit a beam of radiation into the effluent sample, the photodetector is configured to receive radiation after illuminating the effluent sample, and the processor is configured to analyze the radiation after illuminating the effluent sample and determine an amount of radiation absorbed by the effluent sample. In this and other embodiments, the photodetector can be, for example, a standard photodiode, a CCD camera, a photodiode coupled to a computer-controlled optical filter, or several photodiodes closely arranged and having different optical filters.

[0014] In other related embodiments, the optical system is further configured to measure light scattering caused by the effluent sample. Here, the light source is configured to emit a beam of radiation into the effluent sample, the photodetector is configured to receive radiation after illuminating the effluent sample, and the processor is configured to analyze the radiation after illuminating the effluent sample and determine an amount of light scattering caused by the effluent sample.

[0015] In other embodiments, the electrical system is further configured to measure one or more electrical parameters of the effluent sample, such as capacitance, resistance, conductivity, complex impedance, impedance, reactance, inductance, permittivity, magnetism, and other related properties. For example, to make such measurements, the first electrode (alone or in combination with another electrode, such as the second electrode) is further configured to induce an electrical current in the effluent sample directly via a direct current or by generating an electric field in the effluent sample via an alternating current, and then sense electrical properties of the effluent sample or parameters related thereto. Here, the electrical system can, for example, induce different electrical currents in the sample, each characterized by a different frequency (typically ranging between 5-1000 kHz). Measuring the signals produced by these induced currents yields a series of electrical properties (e.g., impedance or capacitance spectra), which can in turn be analyzed to determine compounds within the effluent sample.

[0016] In related embodiments, the electrical system further includes a third electrode and a fourth electrode. Here, the system includes, for example, a first set (pair) of electrodes equipped with two electrodes configured to induce an electrical current in the effluent sample, and a second set (pair) of electrodes separated from the first set of electrodes configured to sense electrical properties of the effluent sample.

[0017] In other embodiments, the processor used in the system is further configured to run an algorithm that synthesizes the optical signals and the electrical signals to determine the amount of compounds (e.g., white blood cells, blood cells, proteins such as fibrin, fat particles, triglycerides, chylomicrons, micelles, biomaterials, and derivatives thereof) in the effluent sample. The processor can be included directly on the system or within the PD machine. Alternatively, the processor can be included in the cloud or in a device connected to the PD machine, such as a computer, tablet, or mobile device.

[0018] Most typically, the system described herein is integrated directly with an electromechanical cycler used for PD. For example, the system can be incorporated directly within an electromechanical PD cycler, e.g., the system can be integrated with (or indeed be part of) a portion of the internal tubing (e.g., internal tubing assembly) within the electromechanical cycler. Alternatively, the system is connected to (or indeed be part of) an external tubing (or second tubing) that is external to the cycler, which is connected to the patient and is typically used to drain effluent fluid from the patient’s abdominal cavity.

[0019] In another aspect, the disclosure relates to a system similar to the above, wherein the electrical system is equipped with a first pair of electrodes and a second pair of electrodes, which are attached to the container and arranged to measure electrical characteristics of the effluent sample other than the electrical capacitance (e.g., electrical resistance, electrical conductivity, complex impedance, impedance, reactance, inductance, permittivity, magnetic properties, and related characteristics). Here, the processor runs an algorithm that integrates the optical signals and the electrical signals to characterize the effluent sample.

[0020] In one aspect, the electrodes of the system are optically transparent. In another aspect, the first pair of electrodes induces an electrical current in the effluent sample, and the second pair of electrodes measures an electrical signal of the effluent sample, which is dependent on the induced electrical current in the sample; in different aspects, a single pair of electrodes is configured to (1) induce an electrical current in the effluent sample, and (2) measure an electrical signal of the effluent sample, which is dependent on the induced electrical current in the sample. In yet another aspect, the system can be used to characterize any liquid sample, not just PD effluent.

[0021] The proposed technology has several advantages. Most importantly, the combination of multiple optical measurement techniques and additional electrical measurement techniques into a single measurement system can improve the sensitivity of the system, allowing it to, for example, detect small amounts of white blood cells in PD effluent. In theory, this means that peritonitis in a PD patient can be detected at a very early stage, allowing the clinician to intervene with therapeutic measures (e.g., the administration of antibiotics) to delay the infection. Ultimately, this can allow an ESRD patient to continue with PD, which, as mentioned above, has several advantages over HD. Furthermore, by integrating multiple measurement techniques into a single system, the proposed technology involves sensing different physiological components of the PD effluent, thereby reducing possible false readings (e.g., ‘false negatives’ and ‘false positives’) that can negatively impact clinical intervention. More specifically, optical measurements, particularly optical absorption spectroscopy, are very sensitive to the specific molecular structure of particulate matter. This measurement can be combined with electrical techniques, such as multi-frequency measurement parameters (including impedance, reactance, resistance, and capacitance), which are very sensitive indicators of the presence of particulate matter in PD effluent. Furthermore, this measurement can be combined with optical measurements (particularly optical absorption spectroscopy), which are sensitive to the specific molecular structure of particulate matter. These techniques, combined, provide an effective way of evaluating PD effluent while avoiding false negatives and false positives that could otherwise compromise the measurement results.

[0022] In view of the disclosure herein, and without limiting the scope in any way, a first aspect of the present disclosure is a system for characterizing an effluent sample from a patient receiving peritoneal dialysis (PD). The system includes a container, an optical system, an electrical system, and a processor. The container houses the effluent sample. The optical system includes a light source configured to emit a beam of radiation through the container and to illuminate the effluent sample, and a photodetector configured to detect radiation after illuminating the effluent sample to generate an optical signal. The electrical system includes at least one pair of electrodes. The at least one pair of electrodes is attached to the container and is configured to measure an electrical property of the effluent sample to generate a property signal. The processor runs an algorithm configured to synthesize the optical signal and the property signal to characterize the effluent sample.

[0023] In the following, embodiments of the first aspect are presented. Each such embodiment can be combined with any other embodiment listed herein, unless otherwise stated.

[0024] In one embodiment, the container is a cuvette comprising at least two surfaces.

[0025] In one embodiment, each of the at least two surfaces of the cuvette comprises an optically transparent material.

[0026] In one embodiment, the optically transparent material is selected from the group consisting of glass, plastic, ceramic, diamond-based materials, or derivatives thereof.

[0027] In one embodiment, the at least one pair of electrodes is a thin film deposited on at least one of the two surfaces.

[0028] In one embodiment, the thin film is a material that is both optically transparent and electrically conductive.

[0029] In one embodiment, the thin film consists essentially of one of gold, In2O5Sn, or derivatives thereof.

[0030] In one embodiment, the at least one pair of electrodes comprises a first pair of electrodes and a second pair of electrodes.

[0031] In one embodiment, the first surface of the container comprises the first pair of electrodes, which is a first optically transparent electrode pair. The second surface of the container comprises the second pair of electrodes, which is a second optically transparent electrode pair.

[0032] In one embodiment, the light source is configured to emit the beam of radiation through the first optically transparent electrode pair and into the effluent sample. The photodetector is configured to receive radiation after illuminating the effluent sample and then passing through the second optically transparent electrode pair.

[0033] In one embodiment, the electrical system includes a capacitor including two capacitor electrodes. The first pair of optically transparent electrodes is the first pair of capacitor electrodes, and the second pair of optically transparent electrodes is the second pair of capacitor electrodes.

[0034] In one embodiment, the first pair of electrodes and the second pair of electrodes each include an optically transparent opening.

[0035] In one embodiment, the light source is configured to emit a beam of radiation through the first optically transparent opening in the first pair of electrodes and into the effluent sample. The photodetector is configured to receive radiation after illuminating the effluent sample and then passing through the second optically transparent opening in the second pair of electrodes.

[0036] In one embodiment, the optical system is further configured to measure light absorption by the effluent sample.

[0037] In one embodiment, the light source is configured to emit a beam of radiation into the effluent sample, the photodetector is configured to receive radiation after illuminating the effluent sample, and the processor is configured to analyze the radiation after illuminating the effluent sample and determine an amount of radiation absorbed by the effluent sample.

[0038] In one embodiment, the optical system is further configured to measure light scattering caused by the effluent sample.

[0039] In one embodiment, the light source is configured to emit a beam of radiation into the effluent sample, the photodetector is configured to receive radiation after illuminating the effluent sample, and the processor is configured to analyze the radiation after illuminating the effluent sample and determine an amount of light scattering caused by the effluent sample.

[0040] In one embodiment, the electrical property of the effluent sample is selected from the group consisting of resistance, conductivity, complex impedance, impedance, reactance, inductance, permittivity, and magnetism.

[0041] In one embodiment, the at least one pair of electrodes includes a pair of electrodes configured to both induce an electric current in the effluent sample and sense an electrical property of the effluent sample or a parameter related thereto.

[0042] In one embodiment, the at least one pair of electrodes includes a pair of electrodes configured to both induce an electric field in the effluent sample and sense an electrical property of the effluent sample or a parameter related thereto.

[0043] In one embodiment, the electrical system further includes a third electrode and a fourth electrode.

[0044] In one embodiment, the at least one pair of electrodes includes a pair of electrodes configured to induce an electric current in the effluent sample and another pair of electrodes configured to sense an electrical property of the effluent sample.

[0045] In one embodiment, the processor is further configured to run an algorithm configured to synthesize the optical signal and the characteristic signal to determine the amount of the compound in the effluent sample.

[0046] In one embodiment, the compound is selected from the group consisting of leukocytes, blood cells, proteins, fat particles, triglycerides, chylomicrons, micelles, biological material, and derivatives thereof.

[0047] In one embodiment, the system is integrated with an electromechanical cycler for PD.

[0048] In one embodiment, the system is incorporated within an electromechanical cycler.

[0049] In one embodiment, the container is part of a first tubing within an electromechanical cycler.

[0050] In one embodiment, the system is connected to a second tubing that is connected to a patient and configured to drain effluent fluid from the patient’s abdominal cavity and pass it through the container.

[0051] In one embodiment, the container is part of a second tubing.

[0052] In one embodiment, the system communicates the measurements to an electromechanical cycler.

[0053] A second aspect of the present disclosure is a system for characterizing an effluent sample from a patient receiving peritoneal dialysis (PD). The system of the second aspect includes a container, an electrical system, an optical system, and a processor. The container houses the effluent sample. The electrical system includes a first pair of electrodes and a second pair of electrodes, wherein the first pair of electrodes and the second pair of electrodes each include an optically transparent portion, the first pair of electrodes and the second pair of electrodes are attached to the container and configured to measure an electrical characteristic of the effluent sample. The optical system includes a light source and a photodetector. The light source is configured to emit a beam of radiation that passes through the first pair of electrodes and illuminates the effluent sample. The photodetector is configured to detect radiation that illuminates the effluent sample and passes through the second pair of electrodes to generate an optical characteristic of the effluent sample. The processor runs an algorithm configured to synthesize the optical characteristic and the electrical characteristic to characterize the effluent sample.

[0054] A third aspect of the present disclosure is a system for measuring white blood cells from a sample of effluent from a patient receiving peritoneal dialysis (PD). The system of the third aspect includes a container, an electrical system, an optical system, and a processor. The container houses the sample of effluent. The electrical system includes a first pair of electrodes and a second pair of electrodes, both of which are optically transparent and attached to the container, wherein the first pair of electrodes is configured to induce an electrical current in the sample of effluent and the second pair of electrodes is configured to measure an electrical signal of the sample of effluent, the electrical signal being dependent on the electrical current induced in the sample. The optical system includes a light source and a photodetector. The light source is configured to emit a beam of radiation through one of the first pair of electrodes and the second pair of electrodes and to illuminate the sample of effluent. The photodetector is configured to detect the radiation after illuminating the sample of effluent and passing through one of the first pair of electrodes and the second pair of electrodes to generate an optical signal. The processor runs an algorithm configured to synthesize the optical signal and the electrical signal to characterize the sample of effluent.

[0055] A fourth aspect of the present disclosure is a system for characterizing a sample of liquid. The system of the fourth aspect includes a container, an optical system, an electrical system, and a processor. The container houses the sample. The optical system includes a light source and a photodetector. The light source is configured to emit a beam of radiation through the container and to illuminate the sample. The photodetector is configured to detect the radiation after illuminating the sample to generate an optical signal. The electrical system includes at least one pair of electrodes, wherein the at least one pair of electrodes is attached to the container and is configured to measure an electrical property of the sample to generate a property signal. The processor runs an algorithm configured to synthesize the optical signal and the property signal to characterize the sample.

[0056] Additional features and advantages of the disclosed devices, systems, and methods will be described in, and apparent from, the following detailed description and drawings. The features and advantages described herein are not all-inclusive and, in particular, many additional features and advantages will be apparent to one of ordinary skill in the art in view of the drawings and description. Moreover, any particular embodiment does not have to exhibit all of the advantages listed herein. Moreover, it is to be understood that the language used herein has been principally selected for readability and instructional purposes and not to limit the scope of the subject matter. BRIEF DESCRIPTION OF DRAWINGS

[0057] It should be understood that the drawings are only illustrative of typical embodiments and should not be considered as limiting the scope of the disclosure, which will be described and explained with additional specificity and detail by the accompanying drawings. The following drawings are listed in the order of appearance.

[0058] Figure 1 is a schematic diagram showing a PDEAS integrated with a PD machine, which in turn is connected to a patient, according to an embodiment;

[0059] Figure 2 is a schematic diagram of the PDEAS of Figure 1 ;

[0060] Figure 3A is a mechanical drawing showing the sample cell for accommodating the PD effluent in the PDEAS of Figure 2 ;

[0061] Figure 3B is a schematic diagram of a pair of sensing and driving electrodes showing the impedance measurement in the sample cell of Figure 3A ;

[0062] Figure 3C to 3D are a photo of the sample cell itself and a photo integrated with a circuit board, respectively, which controls both the impedance measurement and the optical measurement, of Figure 3A ;

[0063] Figure 4A to 4C is a mechanical drawing of an alternative sample cell according to an embodiment, shown from the front, bottom and side, respectively, of a sample cell having a single pair of electrodes with driving and sensing capabilities;

[0064] Figure 5 is a photo of a section of tubing for transporting PD effluent from the PDEAS according to an embodiment, which is compressed and used during optical measurements;

[0065] Figure 6A to 6B is a graph of the relationship of light transmission versus relative concentration of leukocytes measured at a wavelength of λ = 415 nm and a wavelength of λ = 910 nm, respectively;

[0066] Figure 7 shows the absorption at different wavelengths measured with a CCD-based spectrometer and an AS7262 spectral sensor;

[0067] Figure 8 is a graph of the relationship of light transmission versus time measured from a sample of yeast cells dissolved in an aqueous solution using the optical system used in the PDEAS;

[0068] Figure 9A is a set of graphs of the relationship of light absorption versus frequency measured from a sample of blood dissolved in an aqueous solution using the optical system used in the PDEAS;

[0069] Figure 9B is a graph of the relationship of the amplitude of the absorption peak measured at λ = 60 nm versus the relative concentration of blood dilution, where the data of the graph is extracted from the chart in Figure 9A ;

[0070] Figure 10is a plot of the transmitted laser current and scattered light current measured using the optical system used in the PDEAS versus the percentage of diluted milk in an aqueous solution;

[0071] Figure 11A is a collection of plots of the light absorption versus wavelength measured from a sample of yeast dissolved in an aqueous solution using the optical system used in the PDEAS;

[0072] Figure 11B is a plot of the light absorption versus relative concentration of yeast measured at a wavelength of λ = 688 nm;

[0073] Figure 12 is a plot of the series resistance versus frequency measured from a sample of yeast dissolved in an aqueous solution using the impedance system used in the PDEAS;

[0074] Figure 13 is a plot of the series capacitance versus frequency measured from a sample of yeast dissolved in an aqueous solution using the impedance system used in the PDEAS;

[0075] Figure 14A is a plot of the impedance versus relative concentration of yeast cells, where the data for the plot is extracted from a graph similar to Figure 12 ; and

[0076] Figure 14B is a plot of the series capacitance versus relative concentration of yeast cells, where the data for the plot is extracted from a graph similar to Figure 13 . DETAILED DESCRIPTION

[0077] The detailed description is to be understood as merely exemplary; other examples can be derived from the disclosure 'without departing from the scope of the claims. One skilled in the art could derive numerous alternative embodiments, which would still fall within the scope of the claims.

[0078] Figure 1 A schematic is shown that illustrates multiple PDEAS 12a, 12b integrated with a PD cycler 60 to measure PD effluent from a patient 2, with the specific purpose of characterizing the amount of white blood cells in the effluent, which can be indicative of peritonitis. The PDEAS 12a, 12b can be integrated within the PD cycler 60 (as depicted by PDEAS 12a), attached to the tubing 71 that delivers the PD effluent to the patient's washroom 8 (as depicted by PDEAS 12b), or in any portion of the PD cycler 60 or in a portion that houses the PD effluent in the PD cycler 60. While multiple PDEAS 12a, 12b are shown herein, it should be understood that measuring the PD effluent requires only one PDEAS.

[0079] In each case, the PDEAS 12a, 12b is a compact measurement system that performs one or more of the following measurements on the PD effluent: i) optical spectrum; ii) light scattering, more typically laser light scattering; iii) single or multi-frequency bioimpedance; and iv) optical transmission.

[0080] For example, optical measurements can include focused transmission light for particle concentration and / or turbidity estimation, ratio comparison of transmission light, small angle scattering light, and large angle scattering light at a single wavelength, or ratio comparison of any combination of transmission light and / or scattering light at different light wavelengths for particle size evaluation, optical spectrum for particle type determination by color (e.g., red / white blood cells, proteins, fats, etc.), and other similar optical measurements.

[0081] By combining several optical sensors, different optical properties can be distinguished from one another. For example, estimation of particle concentration (e.g., white blood cells) can be achieved by using focused transmission light. Cells will pass through the light beam and interact with the light (e.g., absorption, lensing effects, etc.), resulting in a change in the measured transmission intensity. Estimation of particle size can be achieved by measuring transmission light and / or scattering light at several different angles. Cell-sized particles scatter primarily at small angles (e.g., 0-10 degrees), while small particles with diameters less than the wavelength of light scatter at larger angles. White and red blood cells are typically larger than the wavelength of visible light and can be assumed to scatter light according to Mie scattering, while chylomicrons and cholesterols (e.g., VLDL, LDL, and HDL) are smaller than the wavelength of light and scatter light according to Rayleigh scattering. Similar particle size estimation can be established by using multiple wavelengths of light across multiple sensors. For example, cell-sized particles are more likely to scatter light at large angles using longer wavelengths (e.g., infrared) than shorter wavelengths (e.g., ultraviolet).

[0082] By measuring light at, for example, 0 degrees, 5 degrees, and 20 degrees, 0 degrees (i.e., transmission light) can be used to estimate the number of blood cells when compared to the incident focused laser beam, and the ratio between 0 degrees, 5 degrees, and 20 degrees can be used to estimate particle size, judging whether the turbidity of the effluent is caused primarily by blood cells or lipoproteins. In embodiments, larger detection angles, such as 45 degrees or 90 degrees, can be used to estimate the presence of increasingly smaller particles. By determining the particle size in the effluent, the effluent can be characterized (as detailed in Table 1 below):

[0083] Particles Diameter (pm) Red blood cells (erythrocytes) 6-8 White blood cells: Neutrophils 10-12 Eosinophils 10-12 Basophils 12-15 Small lymphocytes 7-8 Large lymphocytes 12-15 Monocytes 15-30 Lipoproteins: Chylomicrons 0.1-1 VLDL 0.03-0.09 LDL 0.02-0.025 HDL 0.01-0.02

[0084] Table 1. Size of available particles in human plasma and peritoneal fluid. For reference, the wavelength of visible light is between 0.5 and 0.7 pm.

[0085] Next, a computing system located in the PDEAS 12a, 12b, in the gateway 11 (e.g., a mobile phone), or in the cloud 10 analyzes the information from these measurements to estimate the concentration of white blood cells (e.g., leukocytes) in the PD effluent and the actual color of the PD effluent. The computing system further analyzes this information to determine, in turn, the early onset of an infection (e.g., peritonitis). For example, once this condition is detected, a clinician can provide antibiotics or other medication to the patient to address the condition.

[0086] For example, by incorporating both a white light source and a spectrometer, the color of the absorbed light can be measured. This can be used to determine the color of the effluent, and thus whether the estimated cell count counted by the focused transmission photometer is caused by red blood cells or white blood cells. Additionally, the color of the effluent can be used to detect other complications.

[0087] To enable the PDEAS 12a, 12b to receive the PD effluent, the PD cycler 60 is attached to the patient 2 by a first tubing 7. The tubing 7 is connected to a catheter 5 that is sutured into the patient’s peritoneum by a simple surgical procedure. For example, the catheter 5 can extend from an opening 9 in the clothing of the patient 2 lying on a bed 4. Bags 65, 67 containing different mixtures of PD dialysate are attached to the PD cycler 60 by a set of tubings 69.

[0088] During treatment, typically 2-3 liters of dialysate flow through the set of tubings 69 and the catheter 5, ultimately into the patient’s peritoneum to form a fill volume. The fill volume remains in the abdominal cavity while waste products diffuse from the underlying blood vessels across the peritoneum.

[0089] After a variable period of time (typically 2-6 hours, depending on the treatment), the PD effluent flows out through the catheter, through the set of tubings, and into the PD cycler, where it is measured with the PDEAS 12a, 12b as described above to detect white blood cell concentration or other fluid conditions. Additionally, the PD cycler 60 can include standard components such as a heating system 63 for heating the bags 65, 67 to the patient’s body temperature, a display 61 that allows the patient 2 or a user associated with the patient to control the PD cycler 60, and an internal wireless module configured to transmit information from the PDEAS 12a, 12b to the gateway 11 (as indicated by arrow 75) or to the cloud (as indicated by arrow 73).

[0090] Figure 2 A schematic diagram is shown that illustrates the PDEAS 12 in more detail. In general, it will be appreciated that this system (as described in more detail below) includes optical and electrical sensors to make measurements on the PD effluent as it passes through a cuvette 34 enclosed by an opening 40 in a sample holder 30 (also referred to as a measurement cell 30). Further, while theFigure 2 A number of optical and electrical sensors are shown within the PDEAS 12, but it is understood that one or all of these sensors can be used to measure PD effluent to determine its characteristics, such as its color and white blood cell concentration, or electrical characteristics.

[0091] The PDEAS 12 includes a computer processing unit 13 and a custom circuit board. Advantageously, the circuit board can include an optical detector 14. The optical detector 14 is electrically coupled to the laser light source 24 via an electrical connection 16, and to the computer processing unit 13 via an electrical connection 19. For example, the laser light source 24 is a narrowband laser light source that outputs laser radiation 42 of a given wavelength.

[0092] The PDEAS 12 can also include a light source 18 with an optical detector 54, such as a broadband optical detector and / or a segmented / multiple narrowband detector, to measure the spectrum (similar to the spectrum shown) from the PD effluent. For example, the light source 18 is a white light LED. In the illustrated example, the PDEAS 12 includes two separate light sources, namely the laser light source 24 and the light source 18. These two separate light sources are each configured to pass light (visible or otherwise) through the PD effluent, as described in greater detail herein. These two separate light sources can each be configured to be independently detected, such that the readings of the two separate light sources can be easily determined. Finally, these two separate light sources can be configured to output a single coherent wavelength, or to output different light sources (e.g., different wavelengths, such as red, green, or infrared, different intensities, etc.) to provide multiple light source readings of the overall spectrum. Figure 6A to 6B

[0093] As shown, the laser light source 24 and the optical detector 14 are oriented orthogonally to the light source 18 and the detector 54. It is understood that other orientations are equally contemplated herein. Figure 2

[0094] The light source 18 can be configured to output multiple different iterations of light (e.g., different wavelengths, different intensities, etc.). For example, the light source 18 outputs a first set of radiation 20 (at a first wavelength), and also outputs a second set of radiation 22 (at a second wavelength).

[0095] Thus, as shown, a total of three different radiations are output toward the measurement unit 30: the laser radiation 42, the first set of radiation 20, and the second set of radiation 22. Each of these three radiations is configured to pass through the measurement unit 30. Figure 2

[0096] ​​​That is, the measurement cell 30 includes a metallic holder 32 and an optically transparent cuvette 34 (e.g., a glass sample cell) that encloses the PD effluent flowing through the opening 40. Accordingly, the laser radiation 42, the first set of radiations 20, and the second set of radiations 22 are configured to pass through the transparent cuvette 34 and the PD effluent flowing through the opening 40. The PDEAS 12 also includes a lens system 36a-d. For example, the PDEAS 12 includes a first set of lenses 36a-b configured to receive one or more of the laser radiation 42, the first set of radiations 20, and the second set of radiations 22. Similarly, the PDEAS 12 includes a second set of lenses 36c-d configured to receive one or more of the laser radiation 42, the first set of radiations 20, and the second set of radiations 22 after the radiations pass through the optically transparent cuvette 34 and the PD effluent flowing through the opening 40.

[0097] The PDEAS 12 also includes a first set of sensing / driving electrodes 38a and a second set of sensing / driving electrodes 38b. For example, the first set of sensing / driving electrodes 38a is configured to induce a current in the PD effluent flowing through the opening 40; similarly, for example, the second set of sensing / driving electrodes 38b is configured to detect the current (induced by the first set of sensing / driving electrodes 38a) from the PD effluent flowing through the opening 40. Generally, via the first and second sets of sensing / driving electrodes 38a and 38b, the PDEAS 12 is capable of performing impedance measurements on the PD effluent flowing through the opening 40.

[0098] Each of the first and second sets of sensing / driving electrodes 38a and 38b can be electrically coupled to the impedance circuit 52 (e.g., via electrical connections 50).

[0099] As previously described, the laser radiation 42, the first set of radiations 20, and the second set of radiations 22 pass through the measurement cell 30, respectively. Specifically, each of the laser radiation 42, the first set of radiations 20, and the second set of radiations 22 passes through the PD effluent flowing through the opening 40. The first set of radiations 20 passes through the PD effluent flowing through the opening 40 and then out of the measurement cell 30, as indicated by arrow 48; the first set of radiations 20 can be detected by the optical detector 14. The second set of radiations 22 passes through the PD effluent flowing through the opening 40 and then out of the measurement cell 30, as indicated by arrow 44; the second set of radiations 22 can be detected by the detector 54. The laser radiation 42 passes through the PD effluent flowing through the opening 40 and then out of the measurement cell 30, as indicated by arrow 46; the laser radiation 42 can be detected by the optical detector 14.

[0100] Each of the detector 54 and / or the optical detector 14 can be electrically coupled to the computer processing unit 13. For example, the detector 54 is coupled to the processing unit 13 via electrical connections 56.

[0101] In particular, the computer processing unit 13 controls the photodetector 54 and the light source 18, as indicated by the connection 56. During the measurement, the light source emits broadband radiation (also referred to as 'white light'), which typically includes light frequencies ranging from infrared (e.g., l = 700 nm) to ultraviolet (e.g., l = 200 nm). For example, the light source is typically a light-emitting diode (herein "LED") or a tungsten lamp light source. The white light passes through the window 36b connected to the opening in the sample holder 30, and illuminates the PD effluent within the cuvette 34, as indicated by the solid arrow 22.

[0102] Accordingly, depending on its composition, the PD effluent partially absorbs the white light, resulting in the transmitted radiation indicated by the solid arrow 44. The photodetector 54 detects and digitizes the transmitted radiation, and sends the associated signal to the computer processing unit 13 through the connection 56. In some embodiments, the process is preceded by a similar measurement for forming a dwell time of dialysis solution; in this way, the photodetector 54 determines a 'baseline measurement' or'reference measurement', which, like the transmitted radiation, is digitized and sent as an associated signal to the computing system through the connection. The computer processing unit 13 analyzes the difference between the signals associated with the baseline measurement and the transmitted radiation to determine a spectrum associated with the PD effluent.

[0103] In various embodiments, the computer processing unit 13 analyzes the raw optical data and / or the raw electrical data to make determinations about the PD effluent. The computer processing unit 13 can employ statistical processing, including variance, bias, etc., with or without using a relevant spectral fingerprint, to make determinations about the PD effluent. Additionally or alternatively, the computer processing unit 13 can employ a time-dependent analysis of the raw data signal (e.g., fiducial point identification, beat picking, etc.) to make determinations about the PD effluent. In embodiments, the computer processing unit 13 executes one or more algorithms in communication with a database or lookup table to determine a cell count and make related determinations about the PD effluent. Additionally or alternatively, the computer processing unit 13 can implement a neural network. Further disclosure regarding this analysis is included below.

[0104] In accordance with the teachings herein, the computer processing unit 13 can be configured to process optical signals from the optical system in the PDEAS to determine at least one of a particle concentration, a particle size, a particle type, or a color of the PD effluent ("effluent sample"). Further, the computer processing unit 13 can be configured to process electrical signals from the electrical system in the PDEAS to determine at least one of a particle concentration or a particle type.

[0105] In embodiments, the optical system is configured to emit broadband radiation by the light source 18 and to detect the broadband radiation after it passes through the PD effluent by the photodetector 54 to determine a spectrum representative of the PD effluent.

[0106] In embodiments, the computer processing unit 13 is configured to process the optical signal when the optical signal is representative of a spectrum to determine at least one of a color, a particle type, or a particle concentration of the PD effluent.

[0107] In embodiments, the optical system is configured to emit broadband radiation by the light source 18 and to detect the broadband radiation after it passes through a reference sample of a fluid other than the PD effluent, such as a dialysis fluid, by the photodetector 54 to determine a reference spectrum representative of the reference sample, and the computer processing unit 13 is configured to determine the at least one of a color, a particle type, or a particle concentration of the PD effluent based on a difference between the spectrum and the reference spectrum.

[0108] In embodiments, the optical system is configured to emit narrowband radiation by the light source 24 and to detect the narrowband radiation after it passes through the PD effluent by the photodetector 14 to determine an optical transmission value of the PD effluent, and / or to detect the narrowband radiation after it is scattered by the PD effluent at one or more lateral angles from the direction of the radiation beam entering the PD effluent to determine a scattering amplitude at the one or more lateral angles. As used herein, a lateral angle is a non-zero angle from the direction of the radiation beam entering the PD effluent. The scattering amplitude is representative of an intensity or amplitude of the scattered radiation received by the photodetector at the respective lateral angle.

[0109] In embodiments, the light source 24 is configured to emit narrowband radiation of two or more wavelengths sequentially to determine at least one of an optical transmission value or a scattering amplitude at each of the two or more wavelengths.

[0110] In embodiments, the computer processing unit 13 is configured to process the optical transmission value and / or the scattering amplitude to determine at least one particle size in the PD effluent.

[0111] In embodiments, the computer processing unit 13 is configured to determine at least one particle type in the PD effluent based on the at least one particle size.

[0112] In embodiments, the computer processing unit 13 is further configured to determine a particle concentration of the at least one particle type in the PD effluent based on the optical transmission value and / or the scattering amplitude.

[0113] In embodiments, the particle type is selected from the group consisting of white blood cells, blood cells, proteins, fat particles, triglycerides, chylomicrons, micelles, biomaterials, and derivatives thereof.

[0114] In one embodiment, the measuring unit 30 may be cleaned / sterilized (e.g., the opening 40 may be cleaned / sterilized) between uses of the PDEAS 12. In another embodiment, the measuring unit 30 is part of a disposable kit, such that the measuring unit 30 may be removed (after use) and replaced by another sterilized measuring unit for subsequent use.

[0115] Figure 3A A mechanical drawing is shown, illustrating the mechanism for accommodating... Figure 2 The sample cell 80 contains the PD effluent from the PDEAS12. Specifically, the PD effluent flows from the fluid inlet 87a through the sample cell 80 to the fluid outlet 87b. The sample cell 80 may include windows 84 and 85 disposed on opposite sides of the sample cell 80 to allow light transmission "through" the sample cell 80; it should be understood that the sample cell 80 may include additional windows (e.g., on the back side) not shown. For example, a light source 90a may pass through the window to illuminate the PD effluent within the sample cell 80, which is then detected 90b through window 84.

[0116] In addition to optical measurements, sample cell 80 also provides electrical measurements. For example, sample cell 80 may include a first set of sensing / driving electrodes 89a, 89d and a second set of sensing / driving electrodes 89b, 89c. In an embodiment, the first set of sensing / driving electrodes 89a, 89b is configured to induce a current in the PD effluent flowing through sample cell 80. Similarly, in an embodiment, the second set of sensing / driving electrodes 89c, 89d is configured to detect the current from the PD effluent flowing through sample cell 80 (sensed by the first set of sensing / driving electrodes 89a, 89b). Figure 3A As shown, the first set of sensing / driving electrodes 89a and 89b are disposed "outside" the window 85; in this embodiment, the first set of sensing / driving electrodes 89a and 89b induce a current in the PD effluent flowing through the sample cell 80 via capacitive coupling caused by alternating current. In an alternative embodiment, the first set of sensing / driving electrodes 89a and 89b are disposed "inside" the window 85 so as to induce a current in the PD effluent flowing through the sample cell 80 via direct current. Figure 3A As shown, the second set of sensing / driving electrodes 89c and 89d are located "inside" the window 85.

[0117] In an alternative embodiment, one or more of the windows (such as window 85) include embedded surface electronics, enabling window 85 to sense and / or detect electrical signals without the need for additional electrodes, thereby replacing one or more of electrodes 89a-d.

[0118] Next, Figure 3B A schematic diagram is shown, illustrating the use of Figure 3Asensing and drive electrode pairs for impedance measurements in the sample cell 80. For example, the drive electrodes induce current at first and second drive locations 84b, 84c within the sample cell 80. These induced currents are detected at first and second sense locations 84a, 84d via sense electrodes. As the signal travels from the drive locations to the sense locations, the signal interacts with the PD effluent; thus, the electrical signal detected at the sense locations is different from the initial induced current and at the drive locations because the voltage induced by the induced current depends on the impedance of the fluid. This measured difference is useful for characterizing the PD effluent. In embodiments, four-point measurements (“four-terminal sensing”) are used to reduce the adverse effects of contact resistance.

[0119] Figure 3C to 3D respectively Figure 3A a photograph of the sample cell 80 itself and a photograph of the circuit board integrated with both control impedance measurements and optical measurements. Figure 3C shows the relative dimensions of the sample cell 80. Figure 3D shows the sample cell 80 adjacent to a circuit board 100 configured to control optical components (e.g., light sources) and analyze data (e.g., data from a photodetector). Figure 3D also shows a laser diode focusing assembly 102 that directs focused light through one of the windows of the sample cell 80.

[0120] Figure 4A to 4C shows a mechanical drawing of an alternative sample cell 108 according to embodiments, shown from the front, bottom, and side of the sample cell 108, respectively. The alternative sample cell 108 is configured to increase surface area to improve electrical measurements. With the sample cell 108, PD effluent flows from a fluid inlet 114a through the sample cell 108 to a fluid outlet 114b. The sample cell 108 includes windows 110, 112 disposed on opposite sides of the sample cell 108 to allow light transmission “through” the sample cell 108. In embodiments, each of the windows 110, 112 includes embedded surface electronics such that the windows 110, 112 are capable of inducing and / or sensing electrical signals as a single pair of electrodes without the need for additional electrodes. In alternative embodiments, the sample cell 108 includes access ports for electrodes to access the PD effluent flowing between the windows 110, 112.

[0121] Figure 5is a photograph of a tubing segment 150 according to embodiments for transporting PD effluent from a PDEAS, the tubing segment 150 being compressed and used during optical measurements. For example, PD effluent flows within an interior 156 of the tubing 150, which is a flexible / compressible tubing. To obtain correct optical measurements across the tubing 150, the tubing 150 is compressed between transparent glass windows 158a, 158b. Once compressed, the tubing 150 forms a first plane 154a parallel to the window 158a, such that light 160a can easily pass through the window 158a and the first plane 154a to interact with the effluent within the interior 156 of the tubing 150. Similarly, once compressed, the tubing 150 forms a second plane 154b parallel to the window 158b, such that light 160b can easily pass through the second plane 154b and the window 158b for detection.

[0122] As described earlier herein, the PDEAS 12 includes optical and electrical sensors for measuring PD effluent. For optical measurements, the PDEAS 12 can communicate with a database or lookup table to determine cell counts and make related determinations about the PD effluent. Experimental data has confirmed certain trends and relationships with respect to white blood cell concentration.

[0123] For example, Figure 6A to 6B Graphs showing the relationship of light transmission measured at a wavelength of λ = 415 nm and a wavelength of λ = 910 nm, respectively, with respect to relative concentration of white blood cells. Figure 7 White blood cell absorption measured at different wavelengths is also shown, where measurements were taken using both a CCD-based spectrometer and an AS7262 spectral sensor.

[0124] As Figure 6A to 6B and Figure 7 indicated, the spectrum generally contains frequency-dependent bands associated with both white blood cells and other compounds in PD effluent. To demonstrate this concept, an experiment was performed in which white blood cells suspended in a solution of white blood cells taken from a leukemia cell line (referred to as 'HL60') were systematically diluted in a mixture of simulated PD effluent containing additional substances. The optical absorption spectrum was then determined using the techniques described above at different dilutions ranging from 0 to about 180 cells / μl. The system calculated the light intensity at a number of different bands. Figure 6A and Figure 6B Graphs showing the values measured at λ = 415 nm and λ = 910 nm, respectively.

[0125] These graphs clearly show that the systemic increase in HL60 cell lineage leukocytes reduces transmitted radiation detected by a photodetector in a highly linear manner. As indicated by the dashed line in the graph, a linear regression model can be used to 'fit' the data. This linear regression-based mathematical model can then be deployed within a computing system (e.g., in the form of computer code, such as embedded computer code running on an internal processor). Such a model is typically determined through a series of experiments, such as those used to generate... Figure 6A to 6B Experiments using curves in the model. Ideally, these experiments should be conducted on diverse patient populations with varying ages, races, sexes, weights, heights, and durations of ESRD. Once a model is generated, it can be used to analyze subsequent PD effluent samples to estimate white blood cell concentrations. In other words, PDEAS12 can implement one or more of these linear regression models for subsequent PD effluent analysis and determination.

[0126] Similar spectral-based methods can analyze the overall color of PD effluent, which can then be used by a computational system to estimate other patient conditions. For example, generally red PD effluent will have a spectral band around λ = 685 nm; as mentioned above, this may indicate internal bleeding (e.g., ruptured cyst or its ductal problem) or ovulation or menstruation. Similarly, generally green PD effluent will have a spectral band around λ = 550 nm; this may indicate high triglyceride levels, lymphatic obstruction, pancreatitis, lymphoma, general trauma, or drug abuse. Generally brown or orange PD effluent will have a spectral band around λ = 600 nm; this may indicate the presence of feces in the peritoneum, possibly due to intestinal rupture.

[0127] In this embodiment, the photodetector used to measure the spectrum is a CCD camera equipped with a pixel array. Typically, in this embodiment, transmitted radiation first illuminates an optical element, such as a prism or diffraction grating, which spatially spreads the radiation across the CCD camera, allowing multiple pixels in the array to detect unique wavelengths. The advantage of this method is the simultaneous measurement of multiple optical frequencies, the resolution of which depends on the type of prism or diffraction grating used, the distance between the component and the CCD camera (the greater the distance, the more frequencies are spread), and the pixel density in the CCD camera. While this type of optical measurement is relatively fast and produces high-density spectra, the components used to implement it are typically large and expensive, and may therefore not meet the requirements of conventional PD circulators.

[0128] An alternative approach to measuring spectra is to use small, integrated measurement systems, such as the AMS AS7262 or AMSAS7641 spectral sensors. This component combines a sensitive photodetector with a digitally programmable filter, which can be controlled to allow radiation in specific bands to pass through. For example, by using computer code running on a microprocessor to set registers associated with the AMS component, different radiation bands can be detected sequentially, thus 'pieced together' a spectrum using a limited number of data points (e.g., the AMS AS7262 and AS7641 can detect 6 and 10 unique bands, respectively). Figure 7 The image shows measurements of the same sample (in this case, diluted red blood cells) at different times using a CCD-based spectrometer (solid line) and an AMS AS7262 (discrete triangle markers). These data clearly show that while the resolution of the AMS component is limited compared to the spectrometer, both detection systems produce similar data indicating the spectra corresponding to the red blood cells. The advantages of the AMS component over the spectrometer lie in its relatively small size (only a few square millimeters in area) and low cost (typically less than $5), which may make it more compatible with conventional PD cyclers.

[0129] Therefore, refer to Figure 2 In the example shown, photodetector 54 may include a digital filter (not shown) that is programmable to allow radiation within multiple wavelength ranges to pass through. A controller for photodetector 54 (e.g., computer processing unit 13) may be configured to operate the digital filter to allow radiation within a predetermined wavelength range to pass through sequentially while the light source 18 emits broadband radiation. The controller or another processing unit for photodetector 54 may also be configured to generate a spectrum based on optical data detected separately by photodetector 54 for each of the predetermined wavelength ranges.

[0130] Figure 8 to 11B The additional optical experiments and related data that can be used with the PDEAS12 are shown. For example, Figure 8 A graph showing the relationship between light transmittance and time, measured using the optical system employed in the PDEAS12, from a yeast cell sample dissolved in aqueous solution. As an example, the data were collected using a red laser diode and a glass sample cell. A relatively large laser spot size was used (e.g., the entire width of the cuvette was measured). Generally, milk protein dilutions can be used as a simulant for protein turbidity dialyzing. With increasing protein concentration, light transmittance exhibits a near-quadratic relationship, while scattering (at a 90-degree angle) shows a linear relationship.

[0131] Figure 9A This collection of graphs showing the relationship between light absorption and frequency, measured from blood samples dissolved in aqueous solution using the optical system used in PDEAS, is presented. Figure 9BA plot showing the amplitude of the absorption peak measured at λ = 60 nm versus the relative concentration of blood dilution, where the data for the plot was extracted from the graph in Figure 9A This experimental data can be used for analysis and characterization of PD effluent by PDEAS 12.

[0132] Figure 10 to 11B Additional experimental results are included. Namely, Figure 10 A plot showing the transmitted laser current and scattered light current measured with the optical system used in PDEAS 12 versus the percentage of diluted milk in an aqueous solution. Figure 11A A set of plots showing the light absorption versus wavelength measured from a sample of yeast dissolved in an aqueous solution with the optical system used in PDEAS 12. Figure 11B A plot showing the light absorption measured at a wavelength of λ = 68 nm versus the relative concentration of yeast.

[0133] In general, Figure 8 to 11B The optical experiments and related data presented exhibit strong correlations when tested with white blood cells, blood dilution, and yeast cell dilution.

[0134] Additionally and / or alternatively, with respect to electrical measurements, PDEAS 12 can communicate with a database or look-up table to determine cell counts and make related determinations about PD effluent based on one or more of measured resistance, capacitance, bioimpedance, bioelectric reactance, and / or resonant frequency. Experimental data has confirmed certain trends and relationships with respect to yeast cell concentration.

[0135] Namely, Figure 12 A plot showing the series resistance measured from a sample of yeast dissolved in an aqueous solution with the impedance system used in PDEAS 12 versus frequency. Figure 13 A plot showing the series capacitance measured from a sample of yeast dissolved in an aqueous solution with the impedance system used in PDEAS 12 versus frequency. Figure 14A A plot showing the impedance versus the relative concentration of yeast cells, where the data for the plot was extracted from a graph similar to that in Figure 12 . Figure 14B A plot showing the series capacitance versus the relative concentration of yeast cells, where the data for the plot was extracted from a graph similar to that in Figure 13 .

[0136] Thus, similar to the optical analysis discussed previously, the electrical measurements can be used to generate a regression model that is fitted to the experimental data. Once the model is generated, the model can be used to analyze subsequent PD effluent samples. That is, the PDEAS 12 can implement one or more of these linear regression models to use the electrical measurements discussed herein for subsequent PD effluent analysis and determination.

[0137] It will be appreciated that all of the disclosed methods and procedures described herein can be implemented using one or more computer programs or components. These components can be configured as a series of computer instructions on any conventional computer-readable medium, including a RAM, ROM, flash memory, magnetic or optical disks, optical memory, or other storage media. The instructions can be configured to be executed by a processor that, in executing the series of computer instructions, performs or facilitates the performance of all or part of the disclosed methods and procedures.

[0138] It will be appreciated that it is also contemplated that a system configured to characterize effluent samples from patients undergoing PD can be configured to include only an optical system according to any aspect or embodiment described herein, or only an electrical system according to any aspect or embodiment described herein.

[0139] As used in this specification (including the claims) the term "and / or," means

[0140] Many of the features and advantages of the present disclosure can be better understood from the written description herein; therefore, the claims are intended to cover all such features and advantages of the disclosure. Moreover, the disclosure has been described in some detail, by way of illustration and example, for purposes of clarity and understanding. As is readily understood by those skilled in the art, numerous other modifications and adaptations of the methods and procedures described herein other than those specifically described can be employed without departing from the essential functionality of the disclosure. Therefore, the disclosure is not limited to the specific examples given, but instead has a full scope as set out in the claims that follow and equivalents thereof.

Claims

1. A system for characterizing effluent samples from patients undergoing peritoneal dialysis PD, the system comprising: Container (30; 80; 108), used to contain the effluent sample; An optical system includes a light source (18, 24) and a photodetector (14, 54), the light source (18, 24) being configured to emit a radiation beam that passes through the container (30; 80; 108) and irradiates the effluent sample, and the photodetector (14, 54) being configured to detect the radiation after irradiating the effluent sample to generate an optical signal. An electrical system includes at least one pair of electrodes (38a, 38b), wherein the at least one pair of electrodes (38a, 38b) are attached to the container (30; 80; 108) and configured to measure the electrical properties of the effluent sample to generate a characteristic signal; as well as The processor (13) runs an algorithm configured to perform integrated processing on the optical signal and the characteristic signal to characterize the effluent sample.

2. The system according to claim 1, wherein, The container (30; 80; 108) is a sample pool comprising at least two surfaces.

3. The system according to claim 2, wherein, Each of the at least two surfaces of the sample cell comprises an optically transparent material.

4. The system according to claim 3, wherein, The optically transparent material is selected from the group consisting of glass, plastics, ceramics, diamond-based materials or their derivatives.

5. The system according to any one of claims 2 to 4, wherein, The at least one pair of electrodes (38a, 38b) is a thin film deposited on at least one of the two surfaces.

6. The system according to claim 5, wherein, The thin film is an optically transparent and conductive material.

7. The system according to claim 5 or 6, wherein, The thin film is mainly composed of one of gold, In2O5Sn or its derivatives.

8. The system according to any one of the preceding claims, wherein, The at least one pair of electrodes includes a first pair of electrodes (38a) and a second pair of electrodes (38b).

9. The system according to claim 8, wherein, The first surface of the container (30; 80; 108) includes the first pair of electrodes (38a), which are first optically transparent electrode pairs, and the second surface of the container (30; 80; 108) includes the second pair of electrodes (38b), which are second optically transparent electrode pairs.

10. The system according to claim 9, wherein, The light source (18, 24) is configured to emit a radiation beam that passes through the first optically transparent electrode pair and enters the effluent sample, and the photodetector (14, 54) is configured to receive the radiation that irradiates the effluent sample and then passes through the second optically transparent electrode pair.

11. The system according to claim 10, wherein, The electrical system includes a capacitor, the capacitor including two capacitor electrodes, wherein the first optically transparent electrode pair is a first capacitor electrode pair, and the second optically transparent electrode pair is a second capacitor electrode pair.

12. The system according to any one of claims 1 to 8, wherein, Both the first pair of electrodes (38a) and the second pair of electrodes (38b) include optically transparent openings.

13. The system according to claim 12, wherein, The light source (18, 24) is configured to emit a radiation beam that passes through a first optically transparent opening in the first pair of electrodes (38a) and enters the effluent sample, and the photodetector (14, 54) is configured to receive radiation that irradiates the effluent sample and then passes through a second optically transparent opening in the second pair of electrodes (38b).

14. The system according to any one of claims 1 to 8, wherein, The optical system is also configured to measure the light absorption of the effluent sample.

15. The system according to claim 14, wherein, The light source (18, 24) is configured to emit a radiation beam into the effluent sample, the photodetector (14, 54) is configured to receive the radiation after irradiating the effluent sample, and the processor (13) is configured to analyze the radiation after irradiating the effluent sample and determine the amount of radiation absorbed by the effluent sample.

16. The system according to any one of claims 1 to 8, 14 or 15, wherein, The optical system is also configured to measure light scattering caused by the effluent sample.

17. The system according to claim 16, wherein, The light source (18, 24) is configured to emit a radiation beam into the effluent sample, the photodetector (14, 54) is configured to receive the radiation after irradiating the effluent sample, and the processor (13) is configured to analyze the radiation after irradiating the effluent sample and determine the amount of light scattering caused by the effluent sample.

18. The system according to any one of the preceding claims, wherein, The electrical properties of the effluent sample are selected from a group consisting of capacitance, resistance, conductivity, complex impedance, impedance, reactance, inductance, dielectric constant, and magnetism.

19. The system according to claim 18, wherein, The at least one pair of electrodes (38a, 38b) includes an electrode pair (38a; 38b) configured to both induce a current in the effluent sample and sense the electrical properties of the effluent sample or parameters related to the electrical properties.

20. The system according to claim 18, wherein, The at least one pair of electrodes (38a, 38b) includes an electrode pair (38a; 38b) configured to both generate an electric field in the effluent sample and sense the electrical properties of the effluent sample or parameters related to the electrical properties.

21. The system according to claim 18, wherein, The at least one pair of electrodes (38a, 38b) includes an electrode pair (38a; 38b) configured to induce a current in the effluent sample and another electrode pair (38b; 38a) configured to sense the electrical properties of the effluent sample.

22. The system according to any one of the preceding claims, wherein, The processor (13) is also configured to run the algorithm, which is configured to perform integrated processing on the optical signal and the characteristic signal to determine the amount of compound in the effluent sample.

23. The system according to claim 22, wherein, The compounds are selected from the group consisting of leukocytes, blood cells, proteins, fat particles, triglycerides, chylomicrons, micelles, biomaterials and their derivatives.

24. The system according to any one of the preceding claims, wherein the system is integrated with an electromechanical cycler (60) for a PD.

25. The system according to claim 24, wherein the system is incorporated into the electromechanical circulation device (60).

26. The system according to claim 24 or 25, wherein, The containers (30; 80; 108) are part of the first pipe within the electromechanical circulation device (60).

27. The system of claim 24, wherein the system is connected to a second conduit (71), the second conduit (71) being connected to a patient and configured to drain outflowing fluid from the patient's abdominal cavity and to allow the outflowing fluid to pass through the container (30; 80; 108).

28. The system according to claim 27, wherein, The container (30; 80; 108) is part of the second pipe (71).

29. The system according to any one of the preceding claims, wherein the system is configured to transmit measurement results to the electromechanical circulator (60).

30. The system according to claim 1, wherein, The processor (13) is configured to process the optical signal to determine at least one of the particle concentration, particle size, particle type, or color of the effluent sample.

31. The system according to claim 30, wherein, The processor (13) is configured to process the characteristic signal to determine at least one of the particle concentration or the particle type.

32. The system according to claim 30 or 31, wherein, The optical system is configured to emit broadband radiation through the light source (18) and to detect the broadband radiation through the photodetector (54) after the broadband radiation passes through the effluent sample to determine a spectrum representing the effluent sample.

33. The system according to claim 32, wherein, The processor (13) is configured to process the light signal representing the spectrum to determine at least one of the color, particle type, or particle concentration of the effluent sample.

34. The system according to claim 32 or 33, wherein, The optical system is configured to emit broadband radiation through the light source (18) and detect the broadband radiation through the photodetector (54) after the broadband radiation passes through a reference sample of fluid other than the effluent to determine a reference spectrum representing the reference sample, wherein the processor (13) is configured to determine at least one of the color, particle type, or particle concentration of the effluent sample based on the difference between the spectrum and the reference spectrum.

35. The system according to any one of claims 30 to 34, wherein, The optical system is configured to emit narrowband radiation through the light source (24) and to detect the narrowband radiation through the photodetector (14) after the narrowband radiation passes through the effluent sample to determine the light transmittance of the effluent sample, and / or to detect the narrowband radiation at one or more lateral angles to the radiation beam after the radiation beam is scattered by the effluent sample to determine the scattering amplitude at the one or more lateral angles.

36. The system according to claim 35, wherein, The light source (24) is configured to emit narrowband radiation of two or more wavelengths in sequence to determine at least one of the light transmission value or scattering amplitude of each of the two or more wavelengths.

37. The system according to claim 35 or 36, wherein, The processor (13) is configured to process the light transmittance value and / or the scattering amplitude to determine at least one particle size in the effluent sample.

38. The system according to claim 37, wherein, The processor (13) is configured to determine at least one particle type in the effluent sample based on the at least one particle size.

39. The system according to claim 38, wherein, The processor (13) is also configured to determine the particle concentration of at least one particle type in the effluent sample based on the light transmittance value and / or the scattering amplitude.

40. The system according to any one of claims 30 to 39, wherein, The particle type is selected from the group consisting of leukocytes, blood cells, proteins, fat particles, triglycerides, chylomicrons, micelles, biomaterials and their derivatives.

41. A system for characterizing effluent samples from patients undergoing peritoneal dialysis PD, the system comprising: Container (108) for containing the effluent sample; An electrical system includes a first pair of electrodes (38a) and a second pair of electrodes (38b), wherein both the first pair of electrodes (38a) and the second pair of electrodes (38b) include optically transparent portions, the first pair of electrodes (38a) and the second pair of electrodes (38b) are attached to the container (108) and configured to measure the electrical properties of the effluent sample; An optical system includes a light source (18, 24) and a photodetector (14, 54), the light source (18, 24) being configured to emit a radiation beam that passes through the first pair of electrodes (38a) and irradiates the effluent sample, and the photodetector (14, 54) being configured to detect the radiation after irradiating the effluent sample and passing through the second pair of electrodes (38b) to generate optical properties of the effluent sample; as well as The processor (13) runs an algorithm configured to comprehensively process the optical and electrical properties to characterize the effluent sample.

42. A system for measuring white blood cells from an effluent sample, said effluent sample being from a patient undergoing peritoneal dialysis PD, said system comprising: Container (108) for containing the effluent sample; An electrical system includes a first pair of electrodes (38a) and a second pair of electrodes (38b), wherein the first pair of electrodes (38a) and the second pair of electrodes (38b) are both optically transparent and attached to the container (108), wherein the first pair of electrodes (38a) is configured to induce a current in the effluent sample, and the second pair of electrodes (38b) is configured to measure an electrical signal of the effluent sample, the electrical signal depending on the current induced in the sample; An optical system includes a light source (18, 24) and a photodetector (14, 54), the light source (18, 24) being configured to emit a radiation beam that passes through one of the first pair of electrodes (38a) and the second pair of electrodes (38b) and irradiates the effluent sample; the photodetector (14, 54) being configured to detect the radiation irradiating the effluent sample and passing through one of the first pair of electrodes and the second pair of electrodes to generate an optical signal; and The processor (13) runs an algorithm configured to perform integrated processing on the optical signal and the electrical signal to characterize the effluent sample.

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